Aripiprazole (Abilify) is an atypical antipsychotic available both as an oral and intramuscular medication. It is used to treat various psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, and autistic disorder.

Seroquel XR is an oral extended-release atypical antipsychotic that is indicated in adults for the treatment of the following: adjunctive therapy to antidepressants in major depressive disorder, acute depressive episodes in bipolar disorder, acute manic or mixed episodes in bipolar I disorder as either monotherapy or adjunct therapy to lithium or divalproex, maintenance treatment of bipolar I disorder as adjunct to lithium or divalproex, and schizophrenia.

Clinical Rational

SchizophreniaPrevious guidelines in the United States, Europe, and the United Kingdom recommended atypical antipsychotics as first-line treatment for schizophrenia, primarily because they were thought to carry a lower potential risk of extrapyramidal side effects. However, updated evidence from systematic reviews and clinical trials suggests that choosing the most appropriate drug and formulation for an individual may be more important than the drug group. These guidelines now reflect less of a preference for one group of antipsychotics over another, acknowledging that all antipsychotics have adverse effects.

The initial choice of antipsychotic medication or the decision to switch to a new antipsychotic should be made on an individual basis, considering prior treatment response, side effect experience; adherence history; relevant medical history, risk factors; individual medication side effect profile; and long-term treatment planning. Generally, antipsychotic medications other than clozapine and olanzapine, are recommended as first-line treatment for persons with schizophrenia experiencing their first acute positive symptom episode.

Atypical antipsychotics, except for clozapine, are not clearly more effective than typical antipsychotics, but they probably have a lower risk of tardive dyskinesia than typical antipsychotics. On the other hand, several atypicals, especially clozapine, olanzapine and, to a lesser extent, quetiapine, have been associated with marked weight gain, metabolic syndrome, and diabetes. Clozapine is the most effective antipsychotic, but it is usually reserved for refractory disease because of its potential for serious hematologic toxicity. Among other atypical drugs, olanzapine may have some slight advantages in terms of efficacy, but its adverse effects on weight and metabolism may be unacceptable for some patients. Ziprasidone and aripiprazole appear to cause the least weight gain. For patients with co-morbid depression, quetiapine may be preferred. Some patients who do not respond to one antipsychotic may respond to another. Long-acting injectable antipsychotics are useful for patients in whom adherence is a problem.

Bipolar DisorderLithium, valproate, or an atypical antipsychotic, alone or in combination with each other, are the drugs of choice for acute manic episodes and for maintenance treatment of bipolar disorder. Carbamazepine is an alternative.

Lithium or quetiapine is preferred for treatment of depression in bipolar disorder. Lamotrigine in combination with lithium is an alternative for maintenance therapy of bipolar disorder, and it is a reasonable alternative to lithium alone or quetiapine for depressive episodes. Long-acting intramuscular risperidone can delay mood disorder relapse in patients with frequent episodes.

Atypical antipsychotics are less likely to produce extrapyramidal side effects than typical antipsychotics used at conventional doses, which is of particular significance in bipolar disorder because of an apparently greater risk of motor side effects, including tardive dyskinesia.

DepressionGuidelines do not consider antipsychotics as a first line treatment of major depressive disorder without psychosis. However, they suggest that psychotic depression typically responds better to the combination of an antipsychotic and an antidepressant medication rather than either component alone, although some research has shown comparable responses for antidepressive treatment or antipsychotic treatment alone.

AutismGuidelines on treatment of autism state that after treatable medical causes and modifiable environmental factors have been ruled out, a therapeutic trial of medication may be considered if the behavioral symptoms cause significant impairment in functioning, and are not responsive to behavioral interventions. In some cases, the diagnosis of a comorbid psychiatric disorder can be made reasonably and the patient can be treated with medications useful for treating the condition. Although most psychotropic medications have been used in children with autism, there is currently insufficient literature to establish consensus regarding an evidence-based approach to pharmacologic management.

Dementia-Related Psychosis (off-label use)Concerns have emerged in recent years regarding the safety of both atypical and typical classes of antipsychotic medications when used in the elderly dementia population. In June 2008, the FDA warned healthcare professionals that both typical and atypical antipsychotics are associated with an increased risk of death in elderly patients being treated for dementia-related psychosis. As a result, a Black Box Warning on increased risk of mortality in these patients appears on the product labeling of all atypical and typical antipsychotic drugs.

The APA Practice Guideline for Treatment of Patients with Alzheimer’s disease and Other Dementias and the NICE guidelines on dementia currently recommend that nonpharmacologic interventions be attempted before a trial of antipsychotic drug therapy and that the interventions attempted be guided by the patient’s level of distress and the risk to the patients and caregiver. In addition, the FDA states that physicians who prescribe antipsychotics to elderly patients with dementia-related psychosis should discuss the risk of increased mortality with their patients, patients’ families, and caregivers.

Antipsychotic drug therapy generally is reserved for patients who have severe symptoms or when associated agitation, combativeness, or violent behavior puts the patient or others in danger. Current evidence indicates that the atypical antipsychotics can provide modest improvement in behavioral manifestations; some evidence suggests that efficacy may be better for psychosis than for other manifestations. Antipsychotic efficacy appears to be similar among available agents and therefore the choice of agent should be based on adverse effect profile and other patient considerations; to minimize adverse effects, the lowest possible effective dose should be used.

Effective 01/01/2013, step therapy is required for new start prescriptions for Abilify/Seroquel XR when purchased at a pharmacy. Sampling will not be acceptable for patient being on stable therapy.

Abilify Coverage Criteria

BCBSMS covers Abilify (aripiprazole) with prior authorization when the member meets all of the criteria for one of the following conditions:

Schizophrenia

Member is 13 years of age or older, and

Member meets one of the following criteria:

Member has tried and failed treatment with, or has a contraindication to, at least one alternative second-generation antipsychotic agents (e.g., olanzapine, quetiapine immediate-release [IR], risperidone), or

Member is stable on Abilify or was started on Abilify during a recent hospitalization or behavioral health residential program and is at increased risk of an adverse clinical outcome with the use of an alternative second-generation agent

Bipolar Disorder

Member is 10 years of age or older, and

Member meets one of the following criteria:

Member has tried and failed treatment with, or has a contraindication to, at least one alternative second-generation antipsychotic agents (e.g., olanzapine, quetiapine IR, risperidone), or

Member is stable on Abilify or was started on Abilify during a recent hospitalization or behavioral health residential program and is at increased risk of an adverse clinical outcome with the use of an alternative second-generation agent

Depression

Member is 18 years of age or older, and

Member will use Abilify in conjunction with antidepressant therapy, and

Member meets one of the following criteria:

Member has tried and failed treatment with, or has a contraindication to, at least two antidepressant agents, or

Provider submits documentation of the clinical inappropriateness of alternative antidepressant therapy, or

Member is stable on Abilify and is at increased risk of an adverse clinical outcome with the use of an alternative agent

Irritability Associated with Autistic Disorder

Member is six years of age or older, and

Member meets one of the following criteria:

Member has tried and failed treatment with, or has a contraindication to, risperidone, or

Provider submits documentation of the clinical inappropriateness of risperidone therapy, or

Member is at increased risk of an adverse clinical outcome with the use of risperidone

Depression with Psychotic Features

Member is six years of age or older, and

Member will use Abilify in conjunction with antidepressant therapy, and

Member has tried and failed treatment with, or has a contraindication to, an antidepressant agent, and

Member meets one of the following criteria:

Member has tried and failed treatment with an antidepressant agent used concurrently with an alternative antipsychotic agent, or

Member is stable on Abilify or was started on Abilify during a recent hospitalization or behavioral health residential program and is at increased risk of an adverse clinical outcome with the use of an alternative agent

Other Conditions

Member is six years of age or older, and

Member has a psychiatric diagnosis, and

Member meets one of the following criteria:

Member has tried and failed therapy with, or has a contraindication to, at least one alternative second-generation antipsychotic agents (e.g., olanzapine, quetiapine IR, risperidone), or

Member is stable on Abilify or was started on Abilify during a recent hospitalization or behavioral health residential program and is at increased risk of an adverse clinical outcome with the use of an alternative second-generation agent

Quantity Limit

BCBSMS will approve a dose of one tablet per day of Abilify

BCBSMS will approve a greater quantity if the member meets one of the following criteria:

The member is already stable on the requested quantity, or

The member needs a greater quantity for short-term dose titration, or

The provider submits documentation supporting the clinical need for a greater quantity or higher dose

Seroquel XRCoverage Criteria

BCBSMS covers Seroquel XR (quetiapine ER) with prior authorization when the member meets all of the criteria for one of the following conditions:

Schizophrenia

Member is 18 years of age or older, and

Member meets one of the following criteria:

Member has tried and failed treatment with, or has a contraindication to, quetiapine immediate-release (quetiapine IR), or

Member is at increased risk of an adverse clinical outcome with the use of quetiapine IR

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.